Fang, Hui
(2009)
Capillary-based Microreactor System Integrated with UHPLC/GC for High Throughput Screening of Catalysts for Organic Reactions.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Catalyst discovery through high throughput screening can greatly take advantage of automated microreactor technology. Quantitative analysis of reaction outcomes is necessary for evaluating catalyst activities and GC and/or LC are common tools. Few microfluidic systems, however, have the capability of automatically screening catalysts in slow reactions with in situ chromatography analysis. Thus, a novel microreactor was developed that integrated sample loading, reaction and online analysis functions in a totally automated format. An autosampler and syringe pump load homogeneous catalysts and reagents. The chemicals are mixed and reacted in a long capillary followed by online analysis, either by GC or UHPLC. The approach of parallel reactions in a flow stream is good for either slow reactions or fast reactions depending on the operation mode. Some palladium and ligand complex catalysts for the Stille reaction were chosen and screened by a stop-flow approach with GC analysis for validation. The screening results were in good accordance with the literature.The first application of this microreactor was to discover peptidic catalysts for the direct aldol reaction. A major difficulty was the poor solubility of peptidic catalysts. This was solved by allowing catalysts to react with one of the aldol substrates to form soluble catalyst adduct, which was then loaded into the microreactor to complete the reaction. This two-step approach was used to screen a diverse set of amino acids and short peptidic catalysts, in which two groups of peptides containing r-Glu and b-Asp residues showed higher activities than other catalysts. The second application was to screen Bronsted or Lewis acid catalysts for an internal cyclization reaction. This reaction can be used to prepare large libraries of amide compounds for drug discovery. A continuous flow approach with online UHPLC analysis was applied to study this relatively fast reaction. The experimental throughput can reach 9 reactions/h. Results showed that strong acids are generally good for conversion and yield. Lanthanide triflate compounds, although having weak acidity, had better conversion and selectivity than other acids. Side reaction analysis by GC-MS and LC-MS indicated that strong and weak Bronsted acids can lead to the formation of different major byproducts.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
30 September 2009 |
| Date Type: |
Completion |
| Defense Date: |
13 May 2009 |
| Approval Date: |
30 September 2009 |
| Submission Date: |
4 June 2009 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Capillary; Catalyst screening; Microreactor; Reactions |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-06042009-163807/, etd-06042009-163807 |
| Date Deposited: |
10 Nov 2011 19:46 |
| Last Modified: |
15 Nov 2016 13:44 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8008 |
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